The new patent-based technologies can be used for both therapeutic, imaging and diagnostic applications opening up the possibility of treating cancers outside of the central nervous system that express the cancer-associated IL-13 receptor, such as melanoma and pancreatic cancer. Malignant glioma, a form of brain tumour, affects upto 17 500 people annually in the US, contributing to a $200 million (€163 million) annual market.
With more than 10 million new cancer cases worldwide this year, cancer clearly remains one of the largest under-served medical markets. Inadequate treatment alternatives, characterised by limited efficacy and high levels of toxic side effects, create an immediate demand for new cancer treatments.
Targepeutics is just one of a number of biopharmaceutical companies responding to this demand with its genetically modified, mutated Interleukin 13 (IL-13) technology platform. The more specific targeting should allow broader and safer application of recombinant cytotoxins than the first generation, wild type IL-13-based compound, hIL13-PE38QQR.
Human interleukin 13 (hIL13) is a 114 amino acid cytokine secreted by activated T cells and is involved in regulating several different physiological responses. Among these, hIL13 has been shown to downregulate the production of cytokines involved in inflammation.
It has also been shown to upregulate expression of major histo-compatibility class II molecules and CD23 on monocytes, and to regulate various aspects of B cell function. In addition to regulating cells of the immune system, IL-13 has also been shown to act on other cell types. For example, IL13 has been shown to modulate expression of vascular cell adhesion mole-cule-1 (VCAM-1) on endothelial cells.
Along with Glioblast-13, a singly mutated IL-13 molecule combined with a derivative of Pseudomonas exotoxin, the IL-13 platform is expected to yield more specific compounds with multiple mutations of the IL-13 molecule incorporated.
Specific for cancer, mutated IL-13s are created to carry cytotoxins or radiation energy to these cancers. These applications seem unlikely using a wild type IL-13, since it targets vital organs as well as the tumour.
"It is satisfying to see the progress on this first generation of targeted cytotoxins that underlines clinically the validity of the target in brain tumours," said Dr Waldemar Debinski, co-founder, chief scientific officer at Targepeutics and inventor of the wild type IL-13-based cytotoxin, hIL13-PE38QQR.
"We believe though that the rational mutations in IL-13 based on the structure-function relationship studies provide much-needed specificity toward cancer cells and thus should provide better clinical results," she added.
The IL-13 platform intends to provide a complete cancer therapy strategy from initial diagnosis, to imaging and then to treatment. Targepeutics scientists intend to apply this platform to combine the targeting molecule, a rationally mutated IL-13, with a cellular toxin. This compound acts as a "smart bomb", delivering the cytotoxin that is specific to cancer cells by local administration through a tiny catheter.
A second application in this platform is to attach a radioisotope suitable for medical imaging to the target molecule (Glio-Image). This compound will be useful in the imaging or diagnostic imaging of high-grade astrocytomas as well as a monthly and then biannual follow-up test after treatment by Glioblast-13 or next generation compound.
This radioactive compound also shows promise as a therapeutic agent as well, being able to deliver cytotoxic radiation energy in a much more specific and localised manner than conventional radiation therapy.
A third application would be a diagnostic kit for brain tumour tissue. An assessment of the compound binding affinity could determine if over-expression of IL-13 is present, marking a high-grade astrocytoma.
A fourth application would be attaching a targeting molecule to a conventional chemotherapeutic or another small molecule with anti-tumour properties. This application yields specific and targeted chemotherapeutics that would have potentially better tumour penetration and a much lesser toxicity.